Preparation of gentamycin sulfate nanoparticles using eudragit rs-100 polymer and evaluation of its physicochemical properties

Ladan Nejati,1,* Nader shakiba maram,2 Amanollah zarei,3

1. Nanotechnology Research Center and School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2. Nanotechnology Research Center and School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3. Marine Pharmaceutical Sciences Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract


Introduction

Gentamicin sulfate is a wide spectrum aminoglycoside antibiotic. due to negligible oral absorption, gentamicin is usually administered parentally for systemic effects. it is believed that nanoparticles can enhance the bioavailability of peptide and protein drugs, by reducing enzymatic degradation of drug in gi tract, more interactions with gi wall, direct transport to bloodstream from intestinal mucus. eudragit rs-100 a biocompatible, ph-sensitive polymer, which could protect sensitive drugs against acidic medium of the stomach. the aim of this study was preparing gentamicin sulfate nanoparticles by using eudragit rs-100 evaluation of its physicochemical properties.

Methods

Gentamicin sulfate nanoparticles were produced, using w1/o/w2 double-emulsion solvent evaporation method. the inner aqueous phase was prepared by dissolving 50mg of drug in 5ml of water. organic phase was prepared by dissolving 50mg of eudragit rs-100 in 15ml of methylene chloride. primary emulsion was prepared by adding droplets of the aqueous phase to the organic phase under homogenizer (22000rpm). w/o/w emulsion was prepared by adding the w/o emulsion to polyvinyl alcohol (0.2%) solution on an ice bath under homogenizer (22000rpm). the prepared emulsion was left on a magnetic stirrer (1000rpm) at room temperature for 3 hours to evaporate methylene chloride. prepared nanoparticle suspension was centrifuged (20000rpm) at 20ºc for 20 minutes. supernatant was used for loading analysis and sediment was washed with water and lyophilized. production yield, entrapment efficiency, particle size, zeta potential, differential scanning calorimetry (dsc) and fourier transform infrared (ftir) spectroscopy were analysed to evaluate the physicochemical properties of nanoparticles.

Results

Nanoparticle production yield was 66.7 %. entrapment efficiency was calculated 88.74%. mean particle size was 216.3nm. zeta potential was +40.5. ftir analysis presented no interactions between drug and polymer. ftir analysis showed 3617cm-1 and 3742cm-1 peaks for nanoparticles, which probably is due to shifting of the stretching peaks of hydroxyl and amine groups of drug at 3431cm-1 and 3038cm-1. on the other hand, the stretching peak at 1733cm-1 is related to shifted carbonyl group of polymer. dsc thermogram analysis of drug, polymer and nanoparticle showed endothermic peaks at 237ºc and 265.5ºc which were the melting points of gentamicin and eudragit rs-100, respectively.

Conclusion

According to entrapment studies, suitable entrapment efficiency was obtained. incomplete drug entrapment could be due to an enhanced drug leakage into the aqueous phase at high loadings, because of water soluble nature of gentamicin. positive zeta potential of nanoparticle was due to entrapment of drug in positively charged eudragit rs-100 and is appropriate for inhibiting nanoparticles aggregation. evaluation of ftir spectra of drug, polymer and nanoparticle presented physical interactions that led to shifting of hydroxyl and amine groups of drug and carbonyl groups of polymer to lower intensities in nanoparticle spectrum. these interactions caused thermal stability if drug and polymer in nanoparticle structure, which was presented in dsc thermogram of nanoparticle with wider endothermic peak of drug melting point at 237ºc compared to gentamicin powder and less sharper peak of eudragit rs-100 melting point at 265.5ºc. overall, preparing gentamicin nanoparticles using eudragit rs-100 led to nanoparticles with appropriate loading efficiency and particle size which are stable and could be studied more to evaluate their property for oral delivery of gentamicin sulfate.

Keywords

nanoparticle, gentamicin sulfate, eudragit rs-100